Skip to main content
ARS Home » Plains Area » Fort Collins, Colorado » Center for Agricultural Resources Research » Soil Management and Sugarbeet Research » Research » Publications at this Location » Publication #425363
Research Project: Genomic Mining of Sugar Beet Crop Wild Relative Germplasm Resources for New Sources of Disease Resistance

Location: Soil Management and Sugarbeet Research

Title: Vibrio cholerae integrates interspecies quorum-sensing signals to regulate virulence

Author
item BOSIRE, ERICK - Cornell University
item ADAMS, MYFANWY - Cornell University
item BITAR, PAULINA - Cornell University
item MURPHY, SHANNON - Cornell University
item SHIN, JUNG-HO - Cornell University
item Chappie, Joshua
item DORR, TOBIAS - Cornell University
item ALTIER, CRAIG - Cornell University

Submitted to: mBio
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 6/16/2025
Publication Date: 7/31/2025
Citation: Bosire, E.M., Adams, M.C., Bitar, P.P., Murphy, S.G., Shin, J., Chappie, J.S., Dorr, T., Altier, C. 2025. Vibrio cholerae integrates interspecies quorum-sensing signals to regulate virulence. mBio. Article e01537-25. https://doi.org/10.1128/mbio.01537-25.
DOI: https://doi.org/10.1128/mbio.01537-25

Interpretive Summary: Cholera is an acute, bacterial diarrheal disease that remains a significant global health threat. Efforts to eradicate cholera have been hampered by an increased incidence of antimicrobial resistance among pathogen populations. The gut chemical environment, driven largely by the microbiota, has been shown to play important roles in the severity of diseases like cholera. Using genetics, biochemistry, and structural modeling, scientists from USDA and Cornell University found that chemical signals normally used for cell-to-cell communication in other gut bacteria can act through multiple mechanisms to repress bacterial virulence and attenuate pathogenesis. These findings provide a framework for new therapeutic interventions that can reduce disease by disrupting the survival and virulence of a key bacterial pathogen.

Technical Abstract: The human gut harbors enormous microbial diversity, which influences the gut’s chemical environment. As the production of virulence factors affects bacterial fitness, Vibrio cholerae has adapted to sense the gut chemical environment to selectively activate virulence factors at permissible intestinal niches. Here, we show that diffusible signal factors (DSFs) canonically used by gut proteobacteria for quorum-sensing communication can repress expression of essential ToxT-dependent virulence factors cholera toxin (ctxAB) and the toxin co-regulated pilus (tcpA-F). Unlike canonical quorum sensing, where DSFs are sensed by two-component systems or cyclic di-GMP-regulated proteins, DSFs target the central AraC-type transcriptional regulator ToxT. The most potent of these molecules is cis-2-hexadecenoic acid, which represses ctxAB and tcpA-F expression by 84-fold and 12-fold, respectively. We find that the length of the carbon chain, the cis-2 double bond, and the carboxylic-acid terminus play important roles in the efficacy of these repressive chemicals. We further demonstrate that these chemicals interact with ToxT, preventing it from binding its target promoters while also rendering it susceptible to degradation. Our findings suggest that c2HDA targets ToxT’s fatty acid-binding pocket, where high-affinity interactions likely maintain a restrained conformation that represses activity. Collectively, our data show that V. cholerae senses interspecies DSF signals to regulate virulence activation, providing an opportunity to design interventions targeting the virulence of this pathogen.